Pyriproxyfen is a pyridine insecticide that mimics juvenile growth hormone, which prevents larvae from developing into reproduction-capable adults. The LD50 of pyriproxyfen in rats is >5,000 mg/kg, >1,300 mg/cubic meter/4 hours, and >2,000 mg/kg through oral, inhalation, or percutaneous dosing, respectively.{34241} It is used as a larvicide in the drinking water of 11 municipalities in Brazil and rumors suggested it may be correlated with the increase in cases of microcephaly in Brazil.{34234} The acceptable daily intake determined by the World Health Organization is 0.3 mg/L.{34240} The prevalence of microcephaly in Brazil is not higher in municipalities that use pyriproxyfen in the water supply, compared with municipalities that use the larvicide Bti.{34234} In addition, in zebrafish, even very high doses (0.1 µg/ml, compared with 0.01 µg/ml used in practice for pest control) pyriproxyfen does not induce microcephaly or other brain malformations.{34235} Formulations containing pyriproxyfen are used for flea control in dogs and as an insecticide for ants.{34236,34239}
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A pyridine insecticide
Formal name: 2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]-pyridine
Synonyms: OMS-3019|S-31183
Molecular weight: 321.4
CAS: 95737-68-1
Purity: ≥98%
Formulation: A crystalline solid
Product Type|Biochemicals|Pesticides|Insecticides||Research Area|Neuroscience||Research Area|Toxicology|Environmental|Agriculture||Research Area|Toxicology|Environmental|Aquatic Systems
The tetracycline repressor (TetR) is a transcriptional regulator which normally binds tightly to its palindromic tetO operator DNA, blocking gene expression.{17508} Tet causes the repressor to dissociate from the DNA, allowing transcription to occur. A novel reverse TetR (revTetR) requires tetracycline as a co-repressor to bind tetO and block transcription.{17509,17510} Anhydrotetracycline (hydrochloride) is a powerful effector in both the tetracycline repressor (TetR) and reverse TetR (revTetR) systems, binding the Tet repressor 35-fold more strongly than Tet.{17508,17511} Moreover, anhydrotetracycline poorly binds the 30S ribosomal subunit, compared to Tet,{17512} so it does not act as a general inhibitor of translation and is a poor antibiotic. Perhaps related to this, the concentration of anhydrotetracycline that inhibits eukaryotic cell growth is more than a 1,000-fold above the dose that alters transcription through TetR.{17508}
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Cyclin-dependent kinases (CDKs) are key regulators of cell cycle progression and are therefore promising targets for cancer therapy. (R)-Roscovitine is a potent inhibitor of Cdk2/cyclin E with an IC50 value of 0.1 µM.{14988} It also inhibits Cdk7/cyclin H, Cdk5/p35, and cell division cycle (cdc)/cyclin B with IC50 values of 0.49, 0.16, and 0.65 µM, respectively.{14987,14988,14991} (R)-Roscovitine inhibits the growth of rapidly proliferating cells with an average IC50 value of 15.2 µM against a panel of 19 human tumor cell lines.{14988} In murine models of polycystic kidney disease, (R)-roscovitine effectively inhibited disease progression at doses of 50-100 mg/kg.{14564}
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The nuclear factor-κB (NF-κB) regulates the expression of numerous genes involved in immunity and inflammation, cellular stress responses, growth, and apoptosis. Resveratrol, a polyphenolic trans-stilbene, is a known inhibitor of the activation of NF-κB and exhibits activity against a wide variety of cancer cells. CAY10512 is a substituted trans-stilbene analog of resveratrol that is 100-fold more potent as measured by antioxidant activity. The IC50 value for inhibition of TNFα-induced activation of NF-κB by CAY10512 is 0.15 µM compared to 20 µM by resveratrol.{14545}
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The PtdIn phosphates play an important role in the generation and transduction of intracellular signals.{8344,4096,14518} PtdIns-(3,4,5)-P3-biotin is an affinity probe which allows the PIP3 to be detected through an interaction with the biotin ligand. This design allows PtdIns-(3,4,5)-P3-biotin to serve as a general probe for any protein with a high affinity binding interaction with inositol-(3,4,5)-triphosphate phospholipids, such as phosphatidylinositol 3-kinase, PTEN, or PH-domain-containing proteins.
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